Diagnostic challenges in progressive familial intrahepatic cholestasis type 3 (PFIC3) misdiagnosed as Wilson’s disease: A systematic review

作者：Eyad Gadour, Bogdan Miuţescu, Mohammed Saad Alqahtani, Deiana Vuletici, Ghassan Elsayed, Ielmina Domilescu, Antonio Facciorusso · 发表于：Advances in Clinical and Experimental Medicine · 年份：2026 · DOI：10.17219/acem/211596 · 被引用次数：1 · 研究领域：Drug Transport and Resistance Mechanisms、Trace Elements in Health、Cholesterol and Lipid Metabolism

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disorder caused by biallelic mutations in the ABCB4 gene, leading to multidrug resistance protein 3 (MDR3) deficiency. PFIC3 often presents with clinical and biochemical features that overlap with Wilson's disease (WD), including hepatic copper accumulation and elevated urinary copper excretion. These similarities contribute to frequent misdiagnosis, resulting in inappropriate chelation therapy and delayed appropriate management. This systematic review examines reported cases of PFIC3 initially misdiagnosed as WD to highlight diagnostic challenges and assess patient outcomes. A comprehensive search across PubMed, ScienceDirect and Google Scholar identified 11 eligible studies involving 16 patients. Most cases were first treated as WD, receiving chelation therapy without clinical improvement. Diagnosis was later revised to PFIC3 following negative ATP7B mutation testing and identification of ABCB4 variants, often via whole-genome sequencing. Upon switching to ursodeoxycholic acid (UDCA), most patients experienced clinical stabilization. The findings underscore the need for heightened awareness of PFIC3 as a differential diagnosis in atypical WD cases, especially when ceruloplasmin is normal and Kayser-Fleischer (KF) rings are absent. Early genetic testing is essential to avoid mismanagement. Further observational studies are warranted to estimate misdiagnosis frequency and guide diagnostic protocols.